The zinc ring finger in the bICPO protein encoded by bovine herpesvirus-1 mediates toxicity and activates productive infection

The bICPO protein encoded by bovine herpesvirus 1 (BHV-1) is believed to ac tivate transcription and consequently productive infection. Expression of f ull-length bICPO protein is toxic in transiently transfected mouse neurobla stoma cells (neuro-2A) in the absence of other viral genes. However, bICPO does not appear to directly induce apoptosis. Although bICPO is believed to be functionally similar to the herpes simplex virus type 1-encoded ICPO, t he only protein domain that is well conserved is a C3HC4 zinc ring finger l ocated near the N terminus of both proteins. Site-specific mutagenesis of t he zinc ring finger of bICPO demonstrated that it was important for inducin g aggregated chromatin structures in transfected cells and toxicity. The zi nc ring finger was also required for stimulating productive infection in bo vine cells and for trans-activating the thymidine kinase (TK) promoter of h erpes simplex virus type 1. Deletion of amino acids spanning 356-677 of bIC PO altered subcellular localization of bICPO and prevented trans-activation of the TK promoter. However, this deletion did not prevent trans-activatio n of the viral genome. Taken together, these studies indicated that bICPO h as several functional domains, including the zinc ring finger, which stimul ate productive infection and influence cell survival.